Mast cell activation syndrome: Current understanding and research needs.

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers. Although several descriptive publications about MCAS exist, there are many gaps in knowledge, resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients remain to be elucidated. Here we summarize the known literature, identify gaps in knowledge, and highlight research needs. Covered topics include contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; mechanistic research; management of typical and refractory symptoms; and MCAS-specific education for patients and health care providers.

Cognitive Impairment and Depression in Mastocytosis: A Synthesis of the Literature.

PURPOSE OF REVIEW: Symptoms of depression and cognitive dysfunction are commonly reported in mastocytosis. The aims of this review paper are to summarize the current literature on cognitive dysfunction and depressive symptoms, elucidate some of the mechanistic pathways underlying depressive symptoms in mastocytosis, identify gaps in the literature, and offer guidance for future research in this area. RECENT FINDINGS: The study of cognition and depression in mastocytosis is in its infancy and the methodological flaws of the current literature limit interpretability. There is preliminary evidence that some individuals with mastocytosis might experience mild deficits in memory. On average, depression symptom scores fell within the mild to moderate or sub-syndromal range. Regrettably, only one study utilized a standardized diagnostic instrument to assess major depressive disorder. The authors' tendency to inaccurately equate depressive symptoms with a diagnosis of major depressive disorder presents a notable issue. The prevalence of cognitive deficits and depression appears to be similar to other chronic illnesses. Future work needs to better characterize cognition and characterize "depression" in this population.

Loneliness and Its Predictors in Rare Versus Common Chronic Illnesses.

BACKGROUND: Loneliness is a growing public health concern associated with substantial negative mental and physical health outcomes. Loneliness is especially relevant for individuals with a chronic illness, perhaps more so if their illness is rare. Little is known about the psychosocial experience of individuals with a rare chronic illness, and whether and how it may differ from the experience of individuals with common chronic illnesses. We compared the magnitude of loneliness in persons with a rare or common chronic illness and examined theoretically guided predictors of loneliness as follows: stigma, illness intrusiveness, social comparison, social support, support from healthcare providers, and self-efficacy. METHOD: Individuals with a chronic illness (common or rare) completed an anonymous online survey (N = 952). RESULTS: Individuals with common chronic illnesses were as lonely as those with a rare chronic illness. Loneliness in both groups was higher than that in population norms. Regression analyses reveal that independent of other predictors, loneliness was especially high among people who feel stigmatized by others, those who have less social support available, and people whose functioning is more disrupted by their illness (all p values < 0.01). CONCLUSION: The similarity of loneliness in these groups reinforces the value of further systematic research to identify the needs of individuals with any type of chronic illness. Study findings highlight the importance of examining internalized stigma and social support as possible targets of intervention to reduce loneliness among individuals with a chronic illness, recognizing some of the unique features and challenges of their disorders, whether common or rare.

Coping, social support, and anxiety in people with mast cell disorders.

BACKGROUND: Mast cell disorders (MCDs) are rare, chronic, debilitating diseases with a varied and complex clinical trajectory that creates challenges to physical and mental health. Reliable estimates of the prevalence of anxiety in this population are largely nonexistent. Furthermore, very little is known on how sufferers' coping efforts affect their emotions and adjustment. Because a person with an MCD cannot eliminate the stressors associated with their chronic illness, it is important to understand what helps them adjust. OBJECTIVE: To document the magnitude of anxiety in those with MCD, their physical symptoms, levels of social support, and ways of coping with the stress of the disease and to evaluate the extent to which symptoms, social support, and coping are associated with anxiety. METHODS: Individuals with MCDs completed an anonymous Internet-based survey (N = 157). RESULTS: More than half of individuals with MCDs in this study found their illness to be very stressful, and nearly a third were experiencing moderate levels of anxiety. Participants who had more frequent and severe physical symptoms reported higher levels of anxiety. Those who reported coping with their problems by using planning strategies and those who felt they had more social support available to them were less anxious; those who used more avoidant strategies to cope were more anxious. CONCLUSION: Based on the current results, and intervention work in other chronic illness groups, it seems likely that coping behaviors are a fruitful target of intervention for patients with MCD to reduce their emotional distress.

Pregnancy-specific coping and changes in emotional distress from mid- to late pregnancy.

Objective: To examine whether pregnancy-specific coping predicts changes in emotional distress from mid- to late pregnancy. Background: There is a need to identify ways of coping that reduce or elevate emotional distress in pregnant women as such distress increases the risk of adverse birth outcomes. Methods: 132 women receiving prenatal care from a university hospital midwifery practice were recruited prior to 25 weeks gestation (M = 19.58, SD = 5.14). The state anxiety version of the State-Trait Personality Inventory (STPI) and the Revised Prenatal Distress Questionnaire (NuPDQ) were administered in mid- (M = 25.7 weeks, SD = 4.55) and late (M = 33.4 weeks, SD = 4.18) pregnancy and the Revised Prenatal Coping Inventory (NuPCI) at the latter timepoint. Results: Factor analysis of the NuPCI identified five distinct, conceptually interpretable types of coping: Prayer/Spirituality, Receiving Social Support, Planning/Preparation, Positive Appraisal, and Avoidant Coping. Avoidant Coping was used least frequently and Positive Appraisal was used most. The STPI and NuPDQ were aggregated to create a measure of emotional distress. After controlling for mid-pregnancy distress, Avoidant Coping predicted greater emotional distress in late pregnancy (ß = .18, R2 = .61, p < .01) and Positive Appraisal predicted lower late pregnancy distress (ß = -.15, R2 = .60, p < .01). Conclusion: This is one of the first studies to demonstrate that specific ways of coping with stress during pregnancy predict changes in pregnant women's emotional distress. The NuPCI is a psychometrically sound self-report instrument to examine coping and its association with emotional distress.

Challenges in Drug and Hymenoptera Venom Hypersensitivity Diagnosis and Management in Mastocytosis.

Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, pruritus, urticaria, abdominal cramping, diarrhea, wheezing, neuropsychiatric symptoms, and anaphylaxis. Up to 50% of patients with mastocytosis report a history of provoked and unprovoked anaphylaxis, with Hymenoptera venom and drugs the most common culprits. NSAIDs, antibiotics, vaccines, perioperative medications, and radiocontrast media are often empirically avoided without evidence of reactions, depriving patients of needed medications and placing them at risk for unfavorable outcomes. The purpose of this review is to highlight the most common agents responsible for adverse drug reactions in patients with mastocytosis, with a review of current epidemiology, diagnosis, and management of drug hypersensitivity and Hymenoptera venom allergy.

Mismatch between subjective and objective dysautonomia.

Autonomic symptom questionnaires are frequently used to assess dysautonomia. It is unknown whether subjective dysautonomia obtained from autonomic questionnaires correlates with objective dysautonomia measured by quantitative autonomic testing. The objective of our study was to determine correlations between subjective and objective measures of dysautonomia. This was a retrospective cross-sectional study conducted at Brigham and Women's Faulkner Hospital Autonomic Laboratory between 2017 and 2023 evaluating the patients who completed autonomic testing. Analyses included validated autonomic questionnaires [Survey of Autonomic Symptoms (SAS), Composite Autonomic Symptom Score 31 (Compass-31)] and standardized autonomic tests (Valsalva maneuver, deep breathing, sudomotor, and tilt test). The autonomic testing results were graded by a Quantitative scale for grading of cardiovascular reflexes, sudomotor tests and skin biopsies (QASAT), and Composite Autonomic Severity Score (CASS). Autonomic testing, QASAT, CASS, and SAS were obtained in 2627 patients, and Compass-31 in 564 patients. The correlation was strong between subjective instruments (SAS vs. Compass-31, r = 0.74, p < 0.001) and between objective instruments (QASAT vs. CASS, r = 0.81, p < 0.001). There were no correlations between SAS and QASAT nor between Compass-31 and CASS. There continued to be no correlations between subjective and objective instruments for selected diagnoses (post-acute sequelae of COVID-19, n = 61; postural tachycardia syndrome, 211; peripheral autonomic neuropathy, 463; myalgic encephalomyelitis/chronic fatigue syndrome, 95; preload failure, 120; post-treatment Lyme disease syndrome, 163; hypermobile Ehlers-Danlos syndrome, 213; neurogenic orthostatic hypotension, 86; diabetes type II, 71, mast cell activation syndrome, 172; hereditary alpha tryptasemia, 45). The lack of correlation between subjective and objective instruments highlights the limitations of the commonly used questionnaires with some patients overestimating and some underestimating true autonomic deficit. The diagnosis-independent subjective-objective mismatch further signifies the unmet need for reliable screening surveys. Patients who overestimate the symptom burden may represent a population with idiosyncratic autonomic-like symptomatology, which needs further study. At this time, the use of autonomic questionnaires as a replacement of autonomic testing cannot be recommended.

Drug and Venom Allergy in Mastocytosis.

Patients with mastocytosis have an increased risk for mast cell activation events including anaphylaxis when exposed to certain drugs and Hymenoptera venom. Hypotension and cardiovascular collapse without skin or other systemic manifestations can occur after Hymenoptera stings, during the perioperative period, and after exposure to nonsteroidal ntiinflammatory drugs, opioids, and other mast cell activating medications, including vancomycin and quinolones. This chapter reviews the epidemiology, mechanisms, diagnosis, management, and treatment options for Hymenoptera venom and drug-induced reactions in patients with mastocytosis.

Cognition in Bipolar Disorder: An Update for Clinicians.

Bipolar disorder is associated with cognitive deficits, which persist across mood states and affect functional outcomes. This article provides an overview of recent progress in measuring cognition in bipolar disorder and its implications for both research and clinical practice. The authors summarize work conducted over the past decade that has helped guide researchers and clinicians in the appropriate measurement of cognitive functioning in bipolar disorder, the design of research studies targeting this domain for treatment, and the implementation of screening and psychoeducational tools in the clinic. Much of this work was conducted by the International Society for Bipolar Disorders Targeting Cognition Task Force. Here, the authors also highlight the need for clinicians to be informed about this aspect of illness and to be equipped with the necessary information to assess, track, and intervene on cognitive problems when appropriate. Finally, the article identifies gaps in the literature and suggests potential future directions for research in this area.

Depression, psychosocial correlates, and psychosocial resources in individuals with mast cell activation syndrome.

Individuals with Mast Cell Activation Syndrome (MCAS), a rare chronic disease, experience unpredictable physical symptoms and diagnostic challenges resulting in poor emotional states. The prevalence and correlates of depressive symptoms were examined among 125 participants who completed the CES-D and relevant instruments. The majority reported a clinically-significant level of depression which was especially common among younger participants and those who reported greater loneliness or more disease-specific stressors. Greater magnitude of depressive symptoms was associated with greater illness intrusiveness, less social support, and lower optimism. Results highlight the value of interventions targeting loneliness and stressors unique to this population.

Immune transcriptional profiles in mothers with clinically elevated depression and anxiety symptoms several years post-delivery.

BACKGROUND: Most research on maternal mental health focuses on the perinatal period and does not extend beyond 12 months postpartum. However, emerging evidence suggests that for some women (30%-50%), psychological symptoms may persist beyond the first year postpartum or even emerge later increasing the risk of chronic mood and anxiety symptoms. Despite the high prevalence rates and devastating maternal-child consequences, studies examining maternal depression, anxiety, and post-traumatic stress disorder (PTSD) beyond the first year postpartum are rare and our understanding of the underlying biological mechanisms is incomplete. Inflammatory processes are thought to be involved in the pathophysiology of depression, anxiety, & PTSD outside of the postpartum period. Therefore, the purpose of the current investigation was to examine the relationship between depression, anxiety, and PTSD two to three years post-delivery, and transcriptional control pathways relevant to inflammatory and antiviral processes. METHODS: Women over 18 years of age enrolled in ongoing research studies at Cedars Sinai Medical Center who were 2-3 years postpartum were invited to participate in the current study. Women (N = 33) reported on their levels of depression, anxiety, and PTSD and provided a blood sample approximately 2-3 years post-delivery. Bioinformatic analyses of differential gene expression (DGEs) to infer transcription factor activity were used. Gene expression was assayed by RNA sequencing and TELiS bioinformatics analysis of transcription factor-binding motifs in the promoters of differentially expressed genes. RESULTS: DGE analyses revealed that women with clinically elevated symptoms of depression, anxiety and PTSD (n = 16) showed upregulation of genes activated by transcription control pathways associated with inflammation (NF-Κ B, p = 0.004; JUN, p = 0.02), including ß-adrenergic responsive CREB (p = 0.01) and reduced activation of genes associated with the antiviral response (IRFs, p = 0.02) and the glucocorticoid signaling pathway (GR, p = 0.02) compared to women without clinical symptoms (n = 17). CONCLUSIONS: This is one of the first investigations into the immune signaling pathways involved in depression, anxiety, and PTSD two to three years post-delivery. The results of this study suggest that clinically elevated symptoms of depression, anxiety, and PTSD two to three years post-delivery are associated with a gene expression profile characterized by upregulated expression of pro-inflammatory genes and downregulated expression of antiviral genes. The data also point to two potential stress responsive pathways linking symptoms to increased inflammatory signaling in immune cells: sympathetic nervous system mediated ß-adrenergic signaling and reduced hypothalamic pituitary adrenal axis activity. Together, these findings highlight the need for investigations into maternal mental health beyond the first year postpartum.

Just relax and you'll get pregnant? Meta-analysis examining women's emotional distress and the outcome of assisted reproductive technology.

RATIONALE: Couples worldwide are seeking treatment for infertility in growing numbers. Both infertility and its treatment are stressful experiences that generate considerable emotional distress. There is speculation that women's distress is associated with poorer likelihood of pregnancy via assisted reproductive technology (ART) and plausible psychobiological mechanisms bolster this association, although prior reviews of existing evidence find little support. A rigorous, comprehensive, and up to date analysis of research on the association of women's distress with ART outcomes is imperative. OBJECTIVE: We systematically searched for and analyzed evidence regarding the association of women's distress before and during treatment with the likelihood of treatment success via ART. METHOD: Meta-analysis using a random-effects model was conducted on prospective studies (k = 20) that compared levels of anxiety, depressive symptoms, or perceived stress before or during ART treatment in women who achieved successful pregnancy outcomes versus those who did not (total N = 4308). RESULTS: Anxiety, depressive symptoms, or perceived stress pre-treatment, and anxiety or depressive symptoms during treatment, were not associated with less favorable ART outcomes. Prior treatment experience, age, and duration of infertility were not significant moderators of these associations. No eligible studies examined perceived stress during treatment. CONCLUSION: Results cast doubt on the belief that distress impedes the success of infertility treatment, offering hope and optimism to the many women who feel emotionally responsible for the outcome of ART and informing the evidence-based practices of their health-care providers. We also identify specific areas and research methods needed to corroborate and extend study conclusions, including study of factors that elevate or attenuate distress in women undergoing infertility treatment.

Psychosocial impact of mast cell disorders: Pilot investigation of a rare and understudied disease.

Mast cell disorders are rare, chronic diseases involving unpredictable physical symptoms ranging in severity, duration, and frequency. Almost two-thirds of participants with these disorders ( n = 180) experienced clinically meaningful depressive symptoms. Depressed mood was associated with somatic symptomatology, poorer quality of life, lower resilience, and indirectly with ways of coping. Newly developed measures for this population performed psychometrically well. There was no gender difference in depression but women reported greater use of several ways of coping, greater disease-related distress, poorer quality of life, and more symptoms. Results underscore the need for further research and development of effective psychosocial interventions for this population.

Patient-provider communication, maternal anxiety, and self-care in pregnancy.

RATIONALE: Favorable relationships with health care providers predict greater patient satisfaction and adherence to provider recommendations. However, the specific components of patient-provider relationships that account for these benefits have not been identified. The potential benefits of strong patient-provider relationships in pregnancy may be especially important, as care providers have frequent, intimate interactions with pregnant women that can affect their emotions and behaviors. In turn, prenatal emotions and health behaviors have potent effects on birth outcomes. OBJECTIVE: This study investigated whether pregnant women's relationships with their midwives predicted better self-care. Specific components of the patient-provider relationship (communication, integration, collaboration, and empowerment) were examined. We also investigated a mechanism through which these relationship components may be associated with salutary health behaviors: by alleviating women's anxiety. METHODS: In total, 139 low-risk patients of a university-affiliated midwifery practice in the northeastern United States completed well-validated measures assessing their relationship with midwives, state anxiety, and prenatal health behaviors in late pregnancy; state anxiety was also assessed in mid-pregnancy. RESULTS: Women's perceptions of better communication, collaboration, and empowerment from their midwives were associated with more frequent salutary health behavior practices in late pregnancy. Controlling for mid-pregnancy anxiety, lower anxiety in late pregnancy mediated associations of communication and collaboration with health behavior practices, indicating that these associations were attributable to reductions in anxiety from mid- to late pregnancy. CONCLUSION: Results substantiate that benefits of patient-provider relationships in pregnancy may extend beyond providing medical expertise. Some aspects of patient-provider relationships may offer direct benefits to pregnant women in promoting better health practices; other aspects of these relationships may indirectly contribute to better health practices by alleviating negative emotions. The benefits of strong midwife relationships may derive from the reassurance, comfort, and warmth these relationships offer, as well as the information and education that midwives provide to their patients.

Psychometric properties of the Prenatal Health Behavior Scale in mid- and late pregnancy.

INTRODUCTION: Psychometrically sound self-report measures are important tools to advance research on health behaviors in pregnancy. The Prenatal Health Behavior Scale (PHBS) has been used in prior studies to quantify health behaviors and examine their associations with relevant variables, but its psychometric properties have not been carefully investigated. METHODS: In a sample of low-risk women, we examined the factor structure, reliability, and validity of the PHBS at mid- (N = 138) and late (N = 102) pregnancy. RESULTS: In confirmatory factor analysis, items on the PHBS loaded onto a single reliable factor, but separating health-promoting and health-impairing behavior into two factors had better model fit. The scales defined by these two factors had good internal consistency in mid- and late pregnancy, were only moderately correlated, and were predicted by somewhat different sets of sociodemographic and psychological variables. Pregnancy-specific stress was a robust predictor of health-promoting and health-impairing behavior across time. DISCUSSION: Results bolster confidence in the reliability and validity of the PHBS and its appropriateness as a self-report tool for investigation of health behaviors among pregnant women. This study is one of the first investigations to examine patterns and predictors of health behavior practices at two time periods of pregnancy.

Psychological and emotional concomitants of infertility diagnosis in women with diminished ovarian reserve or anatomical cause of infertility.

OBJECTIVE: To examine the magnitude and predictors of emotional reactions to an infertility diagnosis in two groups of women: those with diminished ovarian reserve (DOR), and those clinically diagnosed with an anatomical cause of infertility (ACI). DESIGN: Cross-sectional study. SETTING: Academic and private fertility clinics. PATIENT(S): Women diagnosed with DOR (n = 51) and women diagnosed with ACI (n = 51). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Fertility Problem Inventory (infertility distress), Rosenberg Self-Esteem Scale, Health Orientation Scale (emotional reactions to receiving a diagnosis). RESULT(S): Women with DOR had statistically significantly higher infertility distress scores than women with ACI and higher scores on subscales assessing distress from social concerns, sexual concerns, and a need for parenthood. In both groups, higher self-esteem was associated with lower infertility distress. Hierarchical multiple regression analyses revealed that for women with DOR and those with ACI lower infertility distress but not self-esteem predicted a more positive emotional reaction toward receiving a fertility diagnosis. CONCLUSION(S): Women diagnosed with DOR have greater infertility distress but similar self-esteem and emotional reactions to their diagnosis compared with women who have an anatomical cause of infertility. These results suggest that for both groups distress surrounding infertility itself may influence the way women respond to learning the cause of their infertility.